CLL: Value of MRD Testing

Thomas J. Kipps, MD, PhD: We are now testing for what’s called minimal residual disease. What does that mean? Well, patients may get treated and have no clinical signs of having any disease. We can’t see leukemia cells if we look at it under the microscope, but now we have very sensitive tests that can detect 1 cell easily in 100,000 cells and, in some cases, 1 cell in a million. We can detect whether or not there’s a leukemia cell present in 1 in a million cells.

Now obviously, if we’re going to cure this disease, you’d like to eradicate all the leukemia cells. If a patient achieves a very good response—a complete response, for example—and has no detectable minimal residual disease, that can’t be a bad thing. It has to be a good thing. And I think that testing for it can be very worthwhile, particularly if one is trying to achieve a long-lasting remission that may go on for some time. That’s true with chemoimmunotherapy. It could also be true with treatment with some of the newer targeted therapies too. I think that this could also apply to younger patients, or even to older patients, who are going through those types of regimens.

Testing for MRD should be considered for patients who have achieved a good response to treatment, after treatment for which you want to have some sort of idea as to how long the remission might last, particularly for those patients for whom you’re considering stopping treatment.

Typically, patients receiving chemoimmunotherapy are given treatment over a 3-to-6-month period. We hope to achieve a very deep remission, and we recommend that 2-to-3-months after completion of therapy they have a marrow biopsy if they can, because that’s the most sensitive place to look for the presence of minimal residual disease. This can be done on the blood cells, but we know that—particularly if the patients are treated with a monoclonal antibody, such as rituximab or Gazyva, or what’s called obinutuzumab—if you receive an antibody in your treatment regimen, then sometimes you can be fooled by looking at the blood and not see leukemic cells there, even with very sensitive tests. But you look in the marrow, and you may find the leukemic cells lurking.

We like to look, and if we find no leukemic cells with various tests done, at least 1 in 100,000, then it’s excellent, because we see that patients can go on after treatment for months, if not longer—longer than patients who test positive for cells in the marrow. It’s like a weather report. Those patients who clear disease that can be detected in the marrow will have a longer progression-free survival than patients who do clear the leukemic cells from the narrow. And so, that’s why it’s useful. For me, I’d like to know if I had achieved a homerun with therapy, or whether or not I just got on third base or second base. You’d like to know whether or not you made it home.

Transcript Edited for Clarity

Transcript:

Thomas J. Kipps, MD, PhD: We are now testing for what’s called minimal residual disease. What does that mean? Well, patients may get treated and have no clinical signs of having any disease. We can’t see leukemia cells if we look at it under the microscope, but now we have very sensitive tests that can detect 1 cell easily in 100,000 cells and, in some cases, 1 cell in a million. We can detect whether or not there’s a leukemia cell present in 1 in a million cells.

Now obviously, if we’re going to cure this disease, you’d like to eradicate all the leukemia cells. If a patient achieves a very good response—a complete response, for example—and has no detectable minimal residual disease, that can’t be a bad thing. It has to be a good thing. And I think that testing for it can be very worthwhile, particularly if one is trying to achieve a long-lasting remission that may go on for some time. That’s true with chemoimmunotherapy. It could also be true with treatment with some of the newer targeted therapies too. I think that this could also apply to younger patients, or even to older patients, who are going through those types of regimens.

Testing for MRD should be considered for patients who have achieved a good response to treatment, after treatment for which you want to have some sort of idea as to how long the remission might last, particularly for those patients for whom you’re considering stopping treatment.

Typically, patients receiving chemoimmunotherapy are given treatment over a 3-to-6-month period. We hope to achieve a very deep remission, and we recommend that 2-to-3-months after completion of therapy they have a marrow biopsy if they can, because that’s the most sensitive place to look for the presence of minimal residual disease. This can be done on the blood cells, but we know that—particularly if the patients are treated with a monoclonal antibody, such as rituximab or Gazyva, or what’s called obinutuzumab—if you receive an antibody in your treatment regimen, then sometimes you can be fooled by looking at the blood and not see leukemic cells there, even with very sensitive tests. But you look in the marrow, and you may find the leukemic cells lurking.

We like to look, and if we find no leukemic cells with various tests done, at least 1 in 100,000, then it’s excellent, because we see that patients can go on after treatment for months, if not longer—longer than patients who test positive for cells in the marrow. It’s like a weather report. Those patients who clear disease that can be detected in the marrow will have a longer progression-free survival than patients who do clear the leukemic cells from the narrow. And so, that’s why it’s useful. For me, I’d like to know if I had achieved a homerun with therapy, or whether or not I just got on third base or second base. You’d like to know whether or not you made it home.